Parkinson's Disease (hereafter referred to as PD) is the second-most common progressive neurodegenerative disorder, affecting 1% of the population above the age of 65 (Beal, Nat. Rev. Neurosci., 2:325 (2001)) and over 4% by the age of 85 (Giasson and Lee, Neuron 31:885 (2001)). This disease is clinically characterized by slowed movement, resting tremor, rigidity, and postural instability (Beal, 2001). Its characteristic pathologies are the selective degeneration of dopamine-containing neurons in a region of the midbrain (the substantia nigra pars compacta), the formation of cytoplasmic accumulations of aggregated proteins called Lewy bodies (hereafter referred to as LB), and dystrophic neurites (Lewy neurites)(Beal 2001; Giasson and Lee, 2001). There is no proven preventative, restorative, or regenerative therapy for PD, and patients ultimately become quite disabled as a result of this disease (Dawson, Cell 101:115 (2000)).
Because many of the fundamental mechanisms that underlie neuronal death in PD remain unknown, developing suitable methods for studying PD has been difficult. Most cases of PD are sporadic, although specific genetic defects have been identified in several families with rare, inherited forms of the disease (Dawson, 2000). Both environmental and genetic factors are known to play roles in its progression, including oxidative stress and mitochondrial dysfunction, and the genes α-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCHL-1)(Giasson and Lee, 2001).
Recently numerous genes were identified by linkage analysis to rare familial forms of Parkinson's disease. Specifically identified were parkin, alpha-synuclein, and ubiquitin-C-hydrolase-L1 reviewed by Lansbury and Brice, 2002. Thus it is important to understand how genes are associated with loss of neurological function. There is a need to identify the nucleic acids and the functional parts of proteins that cause and modify PD-related symptoms. Thus, there is a need for models that facilitate the discovery and evaluation of therapeutic compositions for predicting, preventing, slowing, and reversing PD. Furthermore, genes that influence PD-related symptoms might vary in sequence among humans, and some variants may increase the predisposition for developing PD and exuberating symptoms. It would also be advantageous to provide a method for detecting an individual's predisposition to PD in order to prevent this condition.